The overall aim of the ADCS is to advance research in the development of interventions that might be useful for treating, delaying, or preventing AD, particularly interventions that might not be developed by industry. In particular, the ADCS has focused on instrument and trial methodology, and the testing of potential therapeutics that might not otherwise be studied by the pharmaceutical industry. For the coming grant cycle, the ADCS will continue its efforts to advance therapeutics through controlled clinical trials, development o novel instruments and trial designs, recruitment efforts (with particular attention to recruitment f minority subjects). The organization will continue its recent emphasis on collaboration and data sharing. Specific Aims: Aim 1: Test interventions to Improve cognition, slow the rate of decline, or delay/prevent the onset of AD. Three of the four projects in this application aim to slow disease progression. Aim 2: Test an intervention to ameliorate behavioral symptoms. We will extend promising early results supporting an adrenergic approach amelioration of behavioral symptoms with a multicenter trial of prazosin. Aim 3: Design new instruments for use in clinical trials. For the present cycle, we have incorporated instrument development into our largest project, the A4 trial. Aim 4: Develop novel and innovative approaches to AD clinical trial design. The A4 trial utilizes a new trial design to test a leading intervention at the earliest feasible stge of disease, preclinical AD. Aim 5: Develop novel and innovative approaches to AD clinical trial analysis. The Biostatistics Core will continue efforts to advance analytical approaches to AD trial design. Work will continue on optimal modeling of longitudinal data, including novel methods to link diverse datasets. Aim 6:.Expand the range of individuals studied in AD studies to include at-risk individuals and those with MCI. The ADCS has focused its methodological research on early-stage trials, and for this cycle, the two largest projects target preclinical AD and mild cognitive impairment. Aim 7: Enhance the recruitment of minority groups into AD studies. For the coming cycle, the ADCS Minority Recruitment Core will expand outreach efforts, and we will require sites to meet minority enrollment targets in our two largest trials.